Document Type
Article
Publication Date
6-22-2017
Publication Title
Chemical Science
Volume
8
Pages
6155-6164
Abstract
The biological fate of amyloid beta (Aβ) species is a fundamental question in Alzheimer’s disease (AD) pathogenesis. The competition between clearance and aggregation of Aβs is critical for the onset of AD. Copper has been widely considered to be an inducer of harmful crosslinking of Aβs, and an important triggering factor for the onset of AD. In this report, however, we present data to show that copper can also be an inducer of Aβ degradation in the presence of a large excess of well-known intrinsic (such as dopamine) or extrinsic (such as vitamin C) anti-oxidants. The degraded fragments were identified using SDS-Page gels, and validated via nanoLC-MS/MS. A tentative mechanism for the degradation was proposed and validated with model peptides. In addition, we performed electrophysiological analysis to investigate the synaptic functions in brain slices, and found that in the presence of a significant excess of vitamin C, Cu(II) could prevent an Aβ-induced deficit in synaptic transmission in the hippocampus. Collectively, our evidence strongly indicated that a proper combination of copper and anti-oxidants might have a positive effect on the prevention of AD. This double-edged function of copper in AD has been largely overlooked in the past. We believe that our report is very important for fully understanding the function of copper in AD pathology.
Recommended Citation
Ye, Hui; Yang, Jing; Zhang, Xueli; Zhu, Yiying; Lenzowski, Emily; Tian, Yanli; Zhang, Can; Hardt, Markus; Qiao, Chunhua; Tanzi, Rudolph E.; Moore, Anna; and Ran, Chongzhao. The Double-Edges Role of Copper in the Fate of Amyloid Beta in the Presence of Anti-Oxidants. Chemical Science, 8, : 6155-6164, 2017. Retrieved from Loyola eCommons, Biology: Faculty Publications and Other Works, http://dx.doi.org/10.1039/C7SC01787A
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Copyright Statement
© Royal Society of Chemistry 2017
Comments
Author Posting. © Royal Society of Chemistry 2017. This article is posted here by permission of the Royal Society of Chemistry for personal use, not for redistribution. The article was published in Chemical Science, vol. 8, 2017, http://pubs.rsc.org/en/content/articlelanding/2017/sc/c7sc01787a#!divAbstract.